MicroRNAs are small non-coding RNAs (ncRNAs), 19-24 nucleotides in length that regulate gene expression, and are aberrantly expressed in most types of cancer. MiRNAs have also been detected in the blood of cancer patients, and can serve as circulating biomarkers. Secreted miRNAs within exosomes can be transferred from cell to cell, and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs.
MicroRNAs (miRNAs) regulate gene expression and interact directly with proteins. Members of the Toll-like receptor family (namely, murine TLR7, and human TLR8) can recognize and bind viral single-stranded RNA (ssRNA) sequences on dendritic cells and B-lymphocytes, leading to cell activation and cytokine production. TLRs are a family of receptors through which the mammalian innate immune system recognizes the presence of invading pathogens. Both murine TLR7 and human TLR8 bind to, and are activated by 20 nucleotide (nt) long single stranded RNAs (ssRNAs), which represent physiological ligands for these two receptors, located in intracellular endosomes.
Cells of various types are known to produce and shed into their surroundings exosomes, also known as microvesicles, microparticles, ectosomes, or argosomes. Exosomes were historically regarded as cellular debris with no apparent function. However, a growing body of experimental data has suggested that exosomes have numerous biological activities. For example, platelet-derived microvesicles were shown to stimulate selected cells via membrane surface proteins (e.g., Thromb. Haemost. (1999), 82:794, or J. Biol. Chem. (1999), 274:7545). In other examples, specific effects of bioactive lipids in platelet microvesicles on certain target cells were reported (e.g., J. Biol. Chem. (2001), 276: 19672; or Cardiovasc. Res. (2001), 49(5):88). In still further examples, platelet microvesicles increased adhesion of mobilized CD34+ endothelial cells by transfer of certain surface components to the mobilized cells (e.g., Blood (2001), 89:3143). More recently, microvesicles have also been shown to comprise RNA that, at least in part, reflects the RNA content of the cell from which the exosome originated.
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